Interleukin-22 regulating Kupffer cell polarization through STAT3/Erk/Akt crosstalk pathways to extenuate liver fibrosis

Su, Si-Biao; Qin, Shanyu; Xian, Xiao-Long; Huang, Feifei; Huang, Qiulan; Zhangdi, Hanjing; Jiang, Hai‐Xing

doi:10.1016/j.lfs.2020.118677

Cited by 20 publications

(18 citation statements)

References 63 publications

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“…Several pathways closely related to liver fibrosis were identified and the phosphorylation levels of STAT3 and AKT were significantly increased in the liver tissues of AKAP12 Δhep mice. Numerous studies have reported that STAT3 acts as an extracellular signaling molecule essential to chronic inflammation and promotes tumorigenesis and tumor-associated inflammation [ [35] , [36] , [37] ]. The PI3K/AKT signaling pathway plays an important regulatory role in the progression of liver fibrosis [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have reported that STAT3 acts as an extracellular signaling molecule essential to chronic inflammation and promotes tumorigenesis and tumor-associated inflammation [ [35] , [36] , [37] ]. The PI3K/AKT signaling pathway plays an important regulatory role in the progression of liver fibrosis [ 37 ]. In addition, activation of the ERK and JNK pathways is significantly positively correlated with activation of hepatic stellate cells, which exacerbates liver fibrosis [ [37] , [38] , [39] , [40] ].…”

Section: Discussionmentioning

confidence: 99%

“…The PI3K/AKT signaling pathway plays an important regulatory role in the progression of liver fibrosis [ 37 ]. In addition, activation of the ERK and JNK pathways is significantly positively correlated with activation of hepatic stellate cells, which exacerbates liver fibrosis [ [37] , [38] , [39] , [40] ]. AKAP12 knockout in hepatocytes activated PI3K-AKT pathway while had little or no effect on the JNK and ERK pathways.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

AKAP12 ameliorates liver injury via targeting PI3K/AKT/PCSK6 pathway

Wang

et al. 2022

Redox Biology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

AKAP12 ameliorates liver injury via targeting PI3K/AKT/PCSK6 pathway

Wang

et al. 2022

Redox Biology

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“…Nevertheless, a great number of studies indicate that the incitation of M1 or M2 macrophages can also exert antifibrotic effects under certain pathological conditions. IL‐22 exerts anti‐inflammatory effects by polarising M2 KCs via STAT3 pathway in CCl4‐induced liver fibrosis 89 . Maresin‐1 (MaR1), a docosahexaenoic acid (DHA) metabolite, triggers M2 activation via the retinoic acid‐related orphan receptor α (RORα)/12‐lipoxygenase (12‐LOX) autoregulatory circuit against inflammation and fibrosis in HFD mice 90 .…”

Section: Hepatic Macrophages In the Regression Of Liver Fibrosismentioning

confidence: 99%

Hepatic macrophages: Key players in the development and progression of liver fibrosis

Cheng

Chai

Wang

et al. 2021

Liver International

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Hepatic fibrosis is a common pathological process involving persistent liver injury with various etiologies and subsequent inflammatory responses that occur in chronic liver diseases. If left untreated, liver fibrosis can progress to liver cirrhosis, hepatocellular carcinoma and eventually, liver failure. Unfortunately, to date, there is no effective treatment for liver fibrosis, with the exception of liver transplantation. Although the pathophysiology of liver fibrosis is multifactorial and includes the activation of hepatic stellate cells, which are known to drive liver fibrogenesis, hepatic macrophages have emerged as central players in the development of liver fibrosis and regression. Hepatic macrophages, which consist of resident macrophages (Kupffer cells) and monocyte‐derived macrophages, have been shown to play an intricate role in the initiation of inflammatory responses to liver injury, progression of fibrosis, and promotion of fibrosis resolution. These features have made hepatic macrophages uniquely attractive therapeutic targets in the fight against hepatic fibrosis. In this review, we synthesised the literature to highlight the functions and regulation of heterogeneity in hepatic macrophages. Furthermore, using the existing findings, we attempt to offer insights into the molecular mechanisms underlying the phenotypic switch from fibrogenic macrophages to restorative macrophages, the regulation of heterogeneity, and modes of action for hepatic macrophages. A better understanding of these mechanisms may guide the development of novel anti‐fibrotic therapies (eg macrophage subset‐targeted treatments) to combat liver fibrosis in the future.

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“…IL-22 injection protects mice against BDL-induced liver fibrosis ( 14 ). In CCl 4 -induced liver fibrosis, IL-22 is capable to slow liver fibrosis progression via an increase in anti-inflammatory KCs to pro-inflammatory-KCs ratio ( 120 ). However, IL-22RA1 knock-out mice develop mild fibrosis in response to CCl 4 treatment, and IL-22/IL-17 inhibition leads to reduced fibrosis ( 105 ).…”

Section: Il-17a Il-22 and Ra In Liver Fibrosismentioning

confidence: 99%

Retinoic Acid: A New Old Friend of IL-17A in the Immune Pathogeny of Liver Fibrosis

2021

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Despite all the medical advances mortality due to cirrhosis and hepatocellular carcinoma, the end stages of fibrosis, continuously increases. Recent data suggest that liver fibrosis is guided by type 3 inflammation with IL-17A at the top of the line. The storage of vitamin A and its active metabolites, as well as genetics, can influence the development and progression of liver fibrosis and inflammation. Retinoic acid (active metabolite of vitamin A) is able to regulate the differentiation of IL-17A+/IL-22–producing cells as well as the expression of profibrotic markers. IL-17A and its pro-fibrotic role in the liver is the most studied, while the interaction and communication between IL-17A, IL-22, and vitamin A–active metabolites has not been investigated. We aim to update what is known about IL-17A, IL-22, and retinoic acid in the pathobiology of liver diseases.

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Interleukin-22 regulating Kupffer cell polarization through STAT3/Erk/Akt crosstalk pathways to extenuate liver fibrosis

Cited by 20 publications

References 63 publications

AKAP12 ameliorates liver injury via targeting PI3K/AKT/PCSK6 pathway

AKAP12 ameliorates liver injury via targeting PI3K/AKT/PCSK6 pathway

Hepatic macrophages: Key players in the development and progression of liver fibrosis

Retinoic Acid: A New Old Friend of IL-17A in the Immune Pathogeny of Liver Fibrosis

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